Sorbitol dehydrogenase inhibitors constitute a class of compounds which have recently become known for their utility in preventing and treating conditions arising from complications of diabetes such as diabetic neuropathy. Such compounds are well known to those skilled in the art and readily identified by standard biological tests.
For example, PCT publication WO 94/07867 discloses methods of inhibiting sorbitol dehydrogenase and thus lowering fructose levels. The methods utilize certain substituted pyrimidines for the control of diabetic complications such as diabetic microangiopathy and diabetic macroangiopathy.
In addition, U.S. Pat. Nos. 5,215,990 and 5,138,058 disclose certain pyrimidine compounds having sorbitol dehydrogenase accumulating activity which are useful as reagents for a pharmacological screening model for testing aldose reductase inhibitors. In particular, U.S. Pat. No. 5,215,990 discloses as Example 2 the compound 4-4-(N,N-dimethylsulfamoyl)piperazino!-2-hydroxymethylpyrimidine.
Joseph R. Williamson et al., "Perspectives in Diabetes, Hyperglycemic Pseudohypoxia and Diabetic Complications", Diabetes, Vol. 42, 801-813, June, 1993 discloses (FIG. 2) "parallels between functional consequences of an increased cystolic NADH/NAD.sup.+ linked to hyperglycemic pseudohypoxia in diabetic tissues and hypoxia or ischemia in myocardial tissue".